Abstract
BackgroundComparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells).ResultsRNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically associating domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species.ConclusionsWe report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.
Highlights
Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals
Substantial efforts are being dedicated to farm animal species, as deciphering the genotype-to-phenotype relationships underlying complex traits such as production efficiency and disease resistance is a prerequisite for exploiting the full potential of livestock [13, 16]
High-depth RNA-seq assays provide gene expression profiles in liver and immune cells from cattle, goat, chicken, and pig For each animal of the four species, we used RNA-seq to profile the transcriptome of liver, CD4+ and CD8+ T cells
Summary
Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. Most complex trait-associated loci lie outside proteincoding regions, and comparative genomics studies have shown that the majority of mammalian-conserved and recently adapted regions consist of non-coding elements [1,2,3]. This evidence prompted the first large-scale efforts into genome annotation for human and model organisms [4,5,6]. Substantial efforts are being dedicated to farm animal species, as deciphering the genotype-to-phenotype relationships underlying complex traits such as production efficiency and disease resistance is a prerequisite for exploiting the full potential of livestock [13, 16]
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